Yehenew M. Agazie, DVM, PhD

Research Interests

Design, chemical synthesis, and testing efficacy of SHP2 inhibitors in breast cancer tumor models.

Agazie laboratory research interests

My laboratory investigates the mechanism of the tyrosine phosphatase SHP2 in mediating dysregulated receptor tyrosine kinase (RTK) and Wnt/β-catenin signaling in breast cancer. Also, my lab investigates the potential of SHP2 as a drug target for the treatment of breast cancer particularly for HER2-positive and triple-negative breast cancer subtypes. The specific areas of focus are:

• Understanding the mechanism of SHP2 in mediating RTK overexpression and signaling in breast cancer.
• Understanding the mechanism of SHP2 in mediating Wnt/β-catenin signaling in breast cancer.
• Defining the biological roles of SHP2 in breast cancer tumorigenesis and metastasis.
• Developing specific SHP2 inhibitors as lead compounds for developing anti-SHP2 drugs.
• Testing efficacy of SHP2 inhibitors in breast cancer tumor models.

Publications that highlight Agazie lab research interests

1. Lade DM, Nicoletti R, Mersch J, Agazie YM. Design and synthesis of improved active-site SHP2 inhibitors with anti-breast cancer cell effects. European journal of medicinal chemistry. 2023;247:115017. Epub 2022/12/31. doi: 10.1016/j.ejmech.2022.115017. PubMed PMID: 36584630.
2. Lade DM, Agazie YM. Targeting SHP2 with an Active Site Inhibitor Blocks Signaling and Breast Cancer Cell Phenotypes. ACS Bio & Med Chem Au. 2023. doi: 10.1021/acsbiomedchemau.3c00024.
3. Hartman Z, Geldenhuys WJ, Agazie YM (2020), Novel Small-Molecule Inhibitor for the Oncogenic Tyrosine Phosphatase SHP2 with Anti-Breast Cancer Cell Effects. Acs Omega. 2020;5(39):25113-24. Epub 2020/10/13. doi: 10.1021/acsomega.0c02746. PubMed PMID: 33043190; PMCID: PMC7542598.
4. Hartman Z, Geldenhuys WJ, Agazie YM (2020), A specific amino acid context in EGFR and HER2 phosphorylation sites enables selective binding to the active site of Src homology phosphatase 2 (SHP2). The Journal of biological chemistry. 2020;295(11):3563-75. Epub 2020/02/07. doi: 10.1074/jbc.RA119.011422. PubMed PMID: 32024694.
5. Martin E, Agazie YM. SHP2 Potentiates the Oncogenic Activity of beta-Catenin to Promote Triple-Negative Breast Cancer. Molecular cancer research : MCR. 2021. Epub 2021/08/15. doi: 10.1158/1541-7786.MCR-21-0060. PubMed PMID: 34389690.
6. Zhao H, Martin E, Matalkah F, Shah N, Ivanov A, Ruppert JM, Lockman PR, Agazie YM. Conditional knockout of SHP2 in ErbB2 transgenic mice or inhibition in HER2-amplified breast cancer cell lines blocks oncogene expression and tumorigenesis. Oncogene. 2019;38 (13):2275-90. PubMed PMID: 30467378; PMCID: PMC6440805.

Publications